Our objective is to understand the role of polyoma T antigens in cell transformation. The middle-size (mT) antigen is associated with two cellular proteins, p60c-src (the cellular homologue of the Rous sarcoma virus transforming protein) and a 61K protein, both of which are implicated in transformation. We will study the nature and function of the association, using modified mT proteins with altered structure and transforming abilities. We will study the modification and enhancement of p60c-src activity as a result of its association with the mT antigen. We will test whether altered mT proteins are able to complement for transformation, using viruses or cloned DNA's encoding mT proteins with altered transforming abilities. We will use retroviral vectors to introduce individual T antigens into cells with high efficiency, and will study the interaction of the cells with purified growth factors to clarify the effects of the T antigens on control of the cell cycle. Some human neuroblastoma cell lines contain p60c-src with enhanced protein kinase activity and N-terminal tyrosine phosphorylation, resembling the p60C-src associated with the mT antigen in polyoma-transformed cells. We will study whether cellular proteins in some tumor cells can form complexes with p60c-src and modify its activity, perhaps contributing to cell transformation and malignancy.